DR. DETLEF SCHUPPAN: Innovating Unprecedented Treatments for Celiac Disease BY MARINA ILYAS, JACOB MARTIN, ESTHER LIM
Detlef Schuppan, MD, PhD, is a professor of Medicine, Gastroenterology, and Hepatology at the Medical Center of the Johannes Gutenberg University and Beth Israel Deaconess Medical Center, Harvard Medical School, and founding director of the Institute for Translational Immunology. He is recognized as a leading expert in celiac disease and his research into celiac disease, fibrotic diseases, cancer and autoimmunity has led to numerous developments in the field. He discovered tissue transglutaminase as an autoantigen in celiac disease in 1997, which led to a paradigm shift in celiac disease research and the development of a highly reliable diagnostic test. In this interview, we hear his perspectives on celiac disease treatment and learn about exciting progress in the field.
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: What is celiac disease, and how does it affect the human body?
: Celiac disease is a nutritional disease that has a fairly well-defined genetic basis. It is an immunological intolerance to gluten proteins in wheat, barley, rye, and related cereals, and these gluten proteins represent about 90% of the cereal proteins present. Gluten is digested to a smaller extent than other food proteins, so everyone has fragments of somewhat intact gluten peptides that reach the small intestine. Part of this is taken up by the gut mucosa, the lining of the gut containing the lamina propria, a connective tissue lining that harbours the largest immune system of the body. Normally, little bits of certain nutrients, like the gluten peptides, get into the lamina propria of the gut wall where the immune system senses them but still maintains a level of active immunosuppression. This means that the gut is primed to have tolerance for foods, which is important for the maintenance of the organism. Hence, normal people without celiac disease will not have an adverse response to gluten. However, it is much harder for people with celiac disease to be tolerant to gluten. Due to a certain genetic predisposition, their bodies recognize gluten peptides as something bad that has to be fended off. After ingestion of gluten, an immune reaction is triggered in the upper small intestine, which leads to intestinal inflammation and the classical signs of celiac disease. When you take biopsies, you see various degrees of atrophy of the villi, which are finger-like protrusions in the small intestine that are important for nutrient uptake. Consequently, their intestines cannot adequately absorb nutrients like minerals, vitamins, and amino acids, which can result in mal-
“Due to a certain genetic predisposition, their bodies recognize gluten peptides as something bad that has to be fended off.”
nutrition, anemia or osteoporosis. This can even lead to intestinal cancer in adults and growth problems in children. Adults diagnosed with late-onset celiac disease often also suffer from other intestinal problems,
